COVID-19 FORCED SCIENTISTS to put vaccine research into warp speed, leading to the vaccines that reshaped how society addressed the pandemic. These messenger RNA (mRNA) vaccines transformed how we prevent COVID-19, and researchers hope they can do the same for cancer.

A new personalized mRNA vaccine has helped prevent recurrence among advanced melanoma patients, according to study results presented April 16 at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, Florida. (The AACR publishes Cancer Today.)

“Vaccine therapies have really been disappointing in the past, but this really provides the first evidence of vaccine therapy working using this neoantigen approach,” said Timothy Yap, AACR Annual Meeting Clinical Trials Committee co-chair and a medical oncologist at the University of Texas MD Anderson Cancer Center in Houston, who was not involved with the study.

While traditional vaccines use a weakened virus to jump-start an immune response, mRNA vaccines instead contain a molecule that produces a protein associated with the virus, according to the Centers for Disease Control and Prevention. The immune system creates antibodies that attack the protein, storing immune memory for later when the virus itself may appear again. When cancer develops, tumor mutations form proteins called neoantigens, so cancer vaccines train the body to recognize these specific proteins as a threat, according to the National Cancer Institute.

The phase II trial involved 157 patients with stage III or IV melanoma who had undergone surgery and were at high risk of recurrence. Participants were randomly assigned to receive either the vaccine and the immunotherapy Keytruda (pembrolizumab) or Keytruda alone. In the experimental group, each participant’s tumor was biopsied, with the sample then undergoing DNA and RNA sequencing before an algorithm determined the proteins involved in each individual’s cancer. After six to seven weeks, patients then received a personalized vaccine based on their specific neoantigens.

After 18 months, 78.6% of the patients who received the vaccine and Keytruda had no cancer recurrence compared with 62.2% of the Keytruda-only group. That equates to a 44% lower risk of recurrence or death for participants receiving the vaccine.

Furthermore, the study found tumor mutational burden did not impact the vaccine’s effectiveness. For each participant, researchers evaluated the number of DNA changes found in their tumor, also known as tumor mutational burden. If a tumor has a high number of mutations, or a high tumor mutational burden, the immune system is more likely to recognize the cancer as a threat and attack it. Because of this, tumor mutational burden typically impacts a vaccine’s effectiveness. However, the study found the vaccine-Keytruda combo similarly lowered recurrence risk for patients with both high and low tumor mutational burden compared with receiving Keytruda alone, according to Ryan Sullivan, one of the study’s authors and the associate director of the Melanoma Program at the Mass General Cancer Center in Boston.

Side effects, such as fatigue, nausea and chills, were mild and consistent across both treatment groups. Those receiving the vaccine had additional side effects similar to those from a COVID-19 vaccination, including injection site pain, but the treatment was generally well tolerated, according to Jeffrey Weber, another of the study’s authors and the deputy director of the NYU Langone Perlmutter Cancer Center in New York City.

“The data are very, very encouraging,” Weber said, but he cautioned the study has collected just two years of follow-up data. He said a phase III trial is slated to begin later this year, which he hopes “will definitively answer the question of whether the vaccine and pembrolizumab causes increased clinical benefit.”

Sullivan noted a significant limitation to this treatment is collecting enough cancerous tissue to produce the individualized vaccine. Some patients, especially those with early-stage disease, have limited tumor tissue available for sampling, making it less likely they could benefit from the vaccine.

While this specific vaccine focused on melanoma, researchers said the science behind it could translate to other cancers. “This approach is absolutely applicable to any solid tumor that expresses neoantigens, and that’s almost every solid tumor,” Weber said, noting particular relevance for treating head and neck, kidney, liver, lung and stomach cancers.

Thomas Celona is the associate editor for Cancer Today.